Toward the end of the period covered in last year's annual report a conclusion of a meeting on poly ICLC held by the NCI was that previous clinical studies have used much too high a level of drug. During the past year we have begun investigating the effects of low doses of poly ICLC on several immune parameters. The details of the type of immune modulation seen appear to be quite dependent on dose level. For example, at very low levels in monkeys, there is seen an increase in % lymphocytes with no change in total WBC, at levels 10X as high (but still lower than we had been using clinically), there is a decrease in % lymphocytes and in total WBC. At the low levels there is activation of both NK cells and macrophage activity, but at the somewhat higher levels, NK activity is decreased, while macrophage activity is still enhanced. The lower level (0.2 mg/m2) is too low to enduce detectable serum interferon; the higher one induces 50-100 Muml of serum. Analysis of data from 3 clinical studies indicates that there is a small, but regular increase in T helper to T suppressor ratio, in addition to enhancing macrophage activity in most patients, and NK activity in a smaller fraction. More detailed studies of these immune alterations in cancer patients, as a function of dose, route and schedule are planned. Studies with USAMRIID, using a virus of military importance Rift Valley Fever Virus, have shown that the drug is effective in protecting against infection both prophylacticaly and therapeutically, and as an adjuvant with RVFV vaccine. Clinical studies with USAMRIID are being discussed, using poly ICLC as an adjuvant with a vaccine, and as a therapeutic agent in volunteers with a self limiting virus.